The objective of this study is to define host and viral contributions to the regulation of the development of coli-phage lambda and related temperate phages. The role of the bacterium, in such virus-host interactions, is being studied by isolating and characterizing a series of bacterial mutants which inhibit the growth of lambda and/or related temperate phages. The technique that we have developed permits the direct selection for mutants which inhibit the activity of specific phage functions. The loci defined by these mutations will be studied in two basic ways: 1) Genetically, by mapping and determining dominance patterns. 2) Functionally, by determining the nature of the product involved. The analysis of phage determined regulation will primarily involve three types of studies: 1) Isolation and characterization of mutant phage which grow on the bacterial mutants. 2) Characterization of transcription termination signals and phage functions which permit violation of such signals. 3) Analysis of molecular rearrangements of the phage genome. Using a well characterized system to define host-virus interactions should have general application in understanding other host-virus interactions, including those involved in lysogenic conversion and malignant transformation. Moreover, a characterization of both the host and viral influences on lambda expression should prove extremely useful in engineering conditions for optimal gene expression by lambda recombinant molecules carrying foreign DNA.